Prostate cancer (CaP) is now the most common cancer in American men, with approximately 180,400 new cases estimated for the year 2000. In 1990, CaP surpassed lung cancer as the most commonly diagnosed cancer among American men. Approximately 189,000 cases, or thirty percent of all newly diagnosed cancers in American men in 2002 will be CaP. One in six American men will be diagnosed with CaP in his lifetime, and this cancer is the second leading cause of cancer deaths in American men with approximately 30,200 deaths estimated for the year 2002.
Ninety percent of CaP cases where the cancer is confined to the prostate (i.e., “organ-confined”) can be cured with surgery if discovered early, but because there is no effective systemic therapy for this disease, the prognosis is poor once the tumor has spread beyond the gland itself and about half of the patients with CaP have clinically advanced (i.e., extraprostatic/extracapsular) disease at the time of initial diagnosis. Even in those patients initially determined to have organ-confined disease, one-third actually have undetected micrometastatic disease, as determined by subsequent pathological staging or disease progression. In all, more than 65% of patients with CaP develop metastatic disease.
Immunotherapy for the treatment of metastatic prostate cancer is based on the activation of the host's immune response against tumor-associated antigens (TAA) present on tumor cells that distinguish them from normal cells. TAA may be normal, tissue-specific cellular proteins that are upregulated on cancer cells, mutated proteins, oncofetal antigens, growth factor receptors, oncogene and tumor-suppressor gene products, among others.
Prostate cancer is an ideal candidate for immunotherapy for many reasons. There is a substantial failure rate of current therapies for the primary tumor and a lack of effective chemotherapy for metastatic disease. The prostate contains organ-specific TAA that can serve as targets of an immune response. Because the prostate is not essential, its removal or destruction in many patients with CaP eliminates the concern for potential autoimmune disease. Moreover, immunotherapies can be directed at metastases without concern regarding the tissue of origin.
One immunotherapeutic approach for cancer involves the use of a patient's tumor cells mixed with various adjuvants, including cytokines, or genetically modified autologous cells that secrete cytokines. Hwang et al., Semin Oncol. 26:192-201 (1999). Among the drawbacks of whole cell vaccines is that it is labor-intensive and time consuming, especially if the cells are to be genetically modified. The success, or the lack of success, in the expansion of primary cultures for autologous vaccines can limit the courses of vaccinations and, further, an autologous vaccine needs to be specifically made for each patien. Simons et al., Semin. Oncol. 25:661-76 (1998). Another strategy for generating antigen-specific immunity is the ex vivo administration of specific antigen or peptides to antigen-presenting cells (APC). Again, this type of therapy is limited by the need to culture cells from each patient and success in the expansion of primary cultures for autologous vaccines can limit the number of courses of vaccination. Furthermore, the use of peptides to “load” APCs faces the obstacle of finding HLA-restricted peptides for all the different polymorphic HLA molecules. (Hwang et al., 1999).
The emergence of prostate cancer (CaP) as a major health issue and the absence of curative treatment for metastatic disease necessitate the development of new treatment modalities.